1,721,026 research outputs found
Pathophysiology of proteinuria and its value as an outcome measure in chronic kidney disease
No full textChronic kidney diseases share common pathogenic mechanisms that, independently from the initial injury, lead to glomerular hyperfiltration, proteinuria, and progressive renal scarring and function loss. Consistent experimental evidence supports the crucial role of proteinuria in accelerating kidney disease progression to end-stage renal failure through multiple pathways, including induction of tubular chemokine expression and complement activation. These events, in turn, lead to inflammatory cell infiltration in the interstitium and sustained fibrogenesis. The extent of proteinuria is widely recognized as a marker of the severity of chronic kidney disease and as a predictor of future decline in glomerular filtration rate. More importantly, a reduction in proteinuria invariably translates into a protection from renal function decline in patients with diabetic and non-diabetic renal disease. Recent evidence also showed the existence of a relatioship between proteinuria levels and cardiovascular risk, which extends to the range of urinary albumin excretion that was previously thought 'normal'. Thus, proteinuria should be considered a valuable surrogate end point for clinical trials in patients with chronic renal diseases and a target for reno- and cardioprotecive strategies
Rituximab in primary membranous nephropathy : first-line therapy, why not?
No full textThe ideal treatment of patients with primary membranous nephropathy (MN) and persistent nephrotic syndrome (NS) is still a matter of debate. This is a major issue since these patients may progress to end-stage kidney disease (ESKD) in 5-10 years. Steroids, alkylating agents, and calcineurin inhibitors have been suggested to achieve NS remission and prevent ESKD in this population. Treatment benefits, however, are uncertain and are often offset by serious adverse events (SAEs). Evidence that B cells play a crucial role in the pathogenesis of the disease, both as precursors of autoantibody-producing cells and as antigen-presenting cells, provided the background for explorative studies testing the role of B cell-depletion therapy with the monoclonal antibody rituximab. This approach aimed at selectively inhibiting disease mechanisms without the devastating consequences of unspecific immunosuppression. Finding that rituximab safely ameliorated NS in 8 patients with primary MN fueled a series of observational studies that uniformly confirmed the safety/efficacy profile of rituximab in this context. Although head-to-head comparisons in randomized clinical trials are missing, comparative analyses between series of homogeneous patient cohorts clearly show at least similar efficacy of rituximab as compared to steroid plus alkylating agents. Moreover, data confirm the dramatically superior safety profile of rituximab that actually appears to be associated with a rate of SAEs even lower than that observed with conservative therapy. Rituximab is also effective in patients resistant to other treatments and its cost-effectiveness is further increased when treatment is titrated to circulating B cells. Recently identified pathogenic antibodies against the M type phospholipase A2 receptor will likely provide a novel tool to monitor disease activity and drive rituximab therapy, at least in a subset of patients. Newly developed anti-CD20 antibodies could represent a valuable option for those who fail rituximab therapy. Steroids, alkylating agents, and calcineurin inhibitors should likely be abandoned
Mechanisms and treatment of CKD
No full textAs CKD continues to increase worldwide, along with the demand for related life-saving therapies, the financial burden of CKD will place an increasing drain on health care systems. Experimental studies showed that glomerular capillary hypertension and impaired sieving function with consequent protein overload play a pathogenic role in the progression of CKD. Consistently, human studies show that proteinuria is an independent predictor of progression and that its reduction is renoprotective. At comparable BP control, inhibitors of the renin-angiotensin system (RAS), including angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), more effectively than non-RAS inhibitor therapy reduce proteinuria, slow progression to ESRD, and even improve the kidney function achieving disease regression in some cases. In participants with diabetes, RAS inhibitors delay the onset of microalbuminuria and its progression to macroalbuminuria, and ACE inhibitors may reduce the excess cardiovascular mortality associated with diabetic renal disease. In addition to RAS inhibitors, however, multimodal approaches including lifestyle modifications and multidrug therapy will be required in most cases to optimize control of the several risk factors for CKD and related cardiovascular morbidity. Whether novel medications may help further improve the cost-effectiveness of renoprotective interventions is a matter of investigation.logy
Recent progress in the pathophysiology and treatment of FSGS recurrence
No full textFocal segmental glomerulosclerosis (FSGS) is a glomerular disease characterized by proteinuria, frequent progression to end-stage renal disease, and recurrence after kidney transplantation in ∼25% of patients, which negatively impacts long-term allograft survival. Experimental studies suggest that abnormalities in T and, possibly, B cells may represent one initial pathogenic trigger, leading to podocyte injury and progressive loss. New data also support the existence of circulating permeability factors able to damage the podocytes, but no single molecule has been consistently identified as the causal pathogenic element in FSGS recurrence. Unfortunately, major progress from mechanistic studies has not translated into substantial advancements in patient treatment, with plasmapheresis (PP) and high doses of cyclosporine (CsA) remaining the mainstays of therapy. Despite consistent experimental and clinical evidence that treatment of proteinuria slows renal function decline in proteinuric nephropathies, maximal use of antiproteinuric agents such as renin angiotensin system antagonists is not routine in the management of FSGS recurrence. More recently, encouraging results have been reported with anti-CD20 depleting antibody rituximab, but further studies are needed to establish its safety/efficacy profile. The authors review recent advancements in understanding the pathophysiology of focal segmental glomerulosclerosis (FSGS) recurrence after kidney transplant and critically discuss the current therapeutic options
Difesa fitosanitaria e sicurezza alimentare
No full textPest management is essential to limit the damages due to the biotic agents of crop losses and obtain adequate yield characterized by high quality standards. Agricultural practice, based on the cultivation of several genetically uniform o very similar crops in contiguous fields, often provides ideal conditions for severe outbreaks of diseases/infestations due to pathogens and insects able to attack the host plant grown in a particular area. Pathogens and insects can cause serious losses, varying from 10 to 40% of the global crop production. Resistant hosts and plant protection products are the control tools most commonly utilized in order to gain effective reduction of crop damages. Since plant protection products can have harmful effects on human health, non-target organisms and environment, their registration and use are regulated in the European Community according to the precautionary principle. Moreover, the European Community countries will implement integrated protection management measures on all cultivated crops starting from 1st January 2014 and use risk indicators in order to define more rational pest management strategie
Old donors for kidney transplantation: how old?
No full textThe widening gap between transplant demand and supply has prompted the expansion of selection criteria for kidney donation to increase the available donor pool. Using kidneys from older donors has increased transplant activity, but has also resulted in reduced graft survival, possibly as a consequence of the imbalance between the number of viable nephrons supplied and the metabolic demand of the recipient. To fill this imbalance and improve graft outcomes, the transplant of 2 older kidneys in the same recipient has been proposed. This procedure, however, does not always confer the same benefit of single transplants from young donors. To optimize allocation of these organs, a panel of pathologists defined a scoring system of pretransplant graft biopsies to help guide the decision between single versus dual kidney transplantation. The survival of kidneys obtained from donors older than 60 years and allocated to single or dual transplantation on the basis of this pretransplant biopsy score was similar to that of single grafts from younger donors and substantially better than that of single grafts from older donors not evaluated histologically before grafting. This strategy has provided excellent outcomes even when kidneys from donors older than 70 years have been used. Thus, biopsy-based allocation algorithm of older grafts may allow extending selection criteria of donors to increase the number of available transplants without increasing the risk of premature graft failure
Targeting the renin angiotensin system in dialysis patients
No full textPatients on chronic dialysis therapy have a dramatic excess cardiovascular risk compared to any other population, including those with overt diabetic nephropathy. Despite this, patients on dialysis are almost invariably excluded from trials evaluating the cardioprotective effect of novel treatments. Consistent evidence is available that inhibitors of the renin-angiotensin system, such as angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs), are more cardioprotective than other antihypertensive agents in patients with chronic renal disease or diabetes (with or without renal involvement), but whether this applies also to patients on dialysis is unknown. However, clear evidence is available that ACE inhibitors and ARBs reduce morbidity and mortality in patients on dialysis with heart failure (HF) or atrial fibrillation (AF). Moreover, these drugs may preserve residual renal function in those with preterminal kidney failure as well as vascular access and peritoneal membrane function in those on extracorporeal or peritoneal dialysis, respectively. These drugs also show an excellent tolerability profile in this population. Thus, ACE inhibitors and ARBs are indicated in patients on dialysis with HF or AF. Available evidence suggests that they should be first-choice therapy in patients on dialysis with hypertension, though trials are still needed to formally demonstrate their superior cardioprotective effect over other antihypertensives in this population
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